Anton J. W. Verplanke

Environmental lead and renal effects in children.

The effect of lead on five renal-effect parameters was studied in 151 children (i.e., 3-6-y-olds) who resided at different distances from a lead smelter in Baia Mare, Romania. A relationship was found between concentration of lead in blood (mean +/- standard deviation: 342 +/- 224 microgram/l) and the activity of N-acetyl-beta-D-glucosaminidase in urine, as demonstrated by a 14% increase of N-acetyl-beta-D-glucosaminidase per 100 micrograms/l blood lead that was indicative of renal tubular damage. No relationship was found between blood lead level and the renal-effect parameters albumin, alpha-1-microglobulin, retinol binding protein, or alanine aminopeptidase in urine. Cadmium in blood was not elevated. It is well known that N-acetyl-beta-D-glucosaminidase is a sensitive parameter for renal effects, resulting from lead exposure in adults and from diabetes and nephrotoxic medicines in children. This study is the first to demonstrate an effect of environmental lead exposure on renal integrity in children.

Biological effect monitoring of occupational exposure to 1,3-dichloropropene: effects on liver and renal function and on glutathione conjugation.

A prospective study was performed in the Dutch flower bulb culture to investigate the possible effects of subchronic exposure to the soil fumigant 1,3-dichloropropene (DCP) on liver and kidney function and on glutathione conjugation capacity in blood. Urine spot samples and venous blood samples from 14 workers applying DCP (applicators) were taken at the start of the season in July, and after the season in October. The parameters of liver function measured were: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, and total bilirubin (conjugated and unconjugated). Total bilirubin was significantly decreased from 9.5 before to 7.0 mumol/l after the season. In combination with an increase in serum gamma-glutamyltranspeptidase activity from 12.5 to 19.5 U/l this indicates moderate hepatic enzyme induction. To study renal function, creatinine and beta 2-microglobulin in serum, and beta 2-microglobulin, albumin, alanine aminopeptidase, beta-galactosidase, and retinol binding protein in urine were measured. The glomerular function parameters albumin in urine and creatinine in serum changed significantly during the season: albumin concentration increased from 5.2 to 7.6 mg/l, whereas creatinine concentration [corrected] decreased from 93.0 to 87.5 mumol/l. The tubular function parameter retinol binding protein also increased in concentration from 20.0 to 26.9 micrograms/l. Therefore, a subclinical nephrotoxic effect of subchronic exposure to DCP cannot be excluded. Effects on glutathione conjugation capacity were studied by measuring erythrocyte glutathione S-transferase activity and blood glutathione concentrations. The activity of glutathione S-transferase in erythrocytes was significantly decreased from 4.7 before to 3.3 U/g haemoglobin after the season. The same was true for the blood glutathione concentrations, which decreased from 0.93 to 0.82 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Occupational exposure to tetrachloroethene and its effects on the kidneys

Occupational exposure to tetrachloroethene (TCE) has been reported to cause early adverse effects on the kidneys. We investigated the effects of TCE exposure on the kidneys in 82 exposed and 19 nonexposed workers from four dry-cleaning shops in The Netherlands. The mean inhaled amount of TCE in the exposed group, which was assessed by determination of its concentration in alveolar air samples, was 8.4 mg/m3 (range, 2.2-44.6 mg/m3). This value corresponds to a mean 8-hour time-weighted average exposure of 7.9 mg/m3 (range, 1-221 mg/m3). A chronic dose index (CDI) was estimated from data on the current TCE dose and the occupational history of the individual subjects. The mean CDI in the exposed group was 400 months X mg/m3 (range, 12-4882 months X mg/m3). Effects on the tubules were assessed with the parameters N-acetyl-beta-D-glucosaminidase, beta-galactosidase, alanine aminopeptidase, and retinol-binding protein (RBP) in urine. Early effects on the glomeruli were monitored with the parameter albumin in urine. Total protein in urine was determined for the general assessment of effects on the glomeruli and tubules. The tubular parameter RBP was increased in the exposed group, compared with the nonexposed group. None of the other parameters differed between the study groups, and none of the renal-effect parameters correlated with the TCE dose or the CDI. In conclusion, occupational exposure to TCE may cause a minor effect on the tubular RBP at exposure levels below the Dutch occupational exposure limit (240 mg/m3).

Dermal absorption of cis-1,3- dichloropropene vapour: human experimental exposure

1. The relevance of skin absorption of cis-1,3-dichloropropene (cis-1,3-DCP) vapour as a route of entry compared to inhalatory uptake has been assessed in human volunteers under controlled exposure conditions. 2. Five adults (four males and one female) were dermally exposed on the forearm and hand during 45 min to 86 mg/m3 cis-1,3-DCP. 3. Dermal uptake was assessed by determination of the main cis-1,3-DCP metabolite in urine: the mercapturic acid conjugate of cis-1,3-DCP (cis-1,3-DCP-MA). 4. When whole-body dermal exposure to vapour is compared to inhalatory exposure, the uptake through the skin is estimated to be about 2-5% of the inhalatory absorption.

Occupational exposure to cis-1,3-dichloropropene: biological effect monitoring of kidney and liver function.

OBJECTIVES To investigate the possible effects of occupational exposure to the nematocide cis-1,3-dichloropropene (cis-DCP) on function of the kidney and liver in the starch potato growing region in The Netherlands. METHODS The study involved 13 commercial application workers exposed tocis-DCP for 117 days, and 22 matched control workers. The inhalatory exposure of the application workers was estimated from biological monitoring data. All workers collected urine and serum samples before, during, and after the fumigation season for monitoring of variables for kidney and liver function. Renal effect variables were alanine aminopeptidase (AAP), N-acetyl-β-D-glucosaminidase (NAG), retinol binding protein (RBP), and albumin (ALB) in urine, and β2-microglobulin (β2M-S) and creatinine in serum (Creat-S). Liver variables were alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) in serum and the urinary ratio of 6-β-hydroxycortisol to free cortisol (βOHC/COR). RESULTS The geometric mean exposure of the application workers was 2.7 mg/m3 (8 hour time weighted average (8 hour TWA)); range 0.1–9.5 mg/m3. No differences were found between the values of the renal effect variables or the liver variables of the exposed group and the control group, except a lower urinary ratio of βOHC/COR in the exposed group. This was not considered to be related to the exposure tocis-DCP. No dose-effect relations were found between the exposure indices and the effect variables. CONCLUSIONS The present study does not provide evidence that occupational exposure tocis-DCP in the starch potato growing region causes adverse effects on the kidney or liver at 8 hour TWA exposure concentrations below 9.5 mg/m3 (2 ppm).

Personal air sampling and biological monitoring of occupational exposure to the soil fumigant cis-1,3-dichloropropene

OBJECTIVES To assess exposure of commercial application workers to the nematocidecis-1,3-dichloropropene (cis-DCP). METHODS The study was conducted during the annual application season, August to 15 November, in the starch potato growing region in The Netherlands. 14 Application workers collected end of shift urine samples on each fumigation day (n=119). The mercapturic acid metabolite N-acetyl-S-(cis-3-chloro-2-propenyl)-L-cysteine (cis-DCP-MA) in urine was used for biological monitoring of the cis-DCP uptake. Inhalatory exposure was assessed by personal air sampling during a representative sample (n=37) of the fumigation days. Extensive information was collected on factors of possible relevance to the exposure and the application workers were observed for compliance with the statutory directions for use. The inhalatory exposure during all fumigation days was estimated from the relation between the personal air sampling data and the biological monitoring data. Exposure levels were correlated with the general work practice. The fumigation equipment and procedures were in accordance with the statutory directions of use, with the exception of the antidrip systems. Two antidrip systems were used: antidrip nozzles or a compressed air system. RESULTS The geometric mean exposure of the application workers was 2.7 mg/m3 (8 hour time weighted average); range 0.1–9.5 mg/m3. On 25 days (21%) the exposure exceeded the Dutch occupational exposure limit (OEL) of 5 mg/m3. This could mainly be explained by prolonged working days of more than 8 hours. The general work practice of the application workers was rated by the observers as good or poor. No difference in exposure to cis-DCP was found in the use of none, one, or two antidrip systems. Malfunctioning of the antidrip systems and lack of experience with the compressed air system were identified as possible causes for the lack of effectiveness of these antidrip systems. The use of personal protection was not always in accordance with the statutory directions of use. Dermal exposure to liquid cis-DCP was found four times during repair and maintenance, but the biological monitoring data did not suggest a significant increase incis-DCP uptake. CONCLUSIONS The application of cis-DCP in the potato growing industry can be performed at exposure concentrations below the Dutch OEL of 5 mg/m3 if the working days are limited to 8 hours. An injector equipped with either kind of antidrip system which is in good working order, as well as the consistent use of personal protection in accordance with the statutory directions of use, may ensure exposure concentrations below the Dutch OEL.

The Determination of α1-Microglobulin by Means of an Automated Latex Immunoassay

Polystyrene (latex) particles coated with human anti-alpha 1 microglobulin antibodies are used in an automated kinetic assay for alpha 1-microglobulin in urine. For values below 12 mg/l, there was no significant difference between two kinds of standard, but above 12 mg/l the results depend on the origin of the alpha 1-microglobulin standard. Correlation between values obtained with both standards was good (r2 = 0.968). The method has a between-run imprecision (CV) of 11-16%. Comparison with two commercial enzyme immunoassays gave a bias of -10% to +40%, while two nephelometric methods differed by 0% to 23%, possibly because the standards used in these methods were of different origin. These results indicate the necessity of standardization of the determination of alpha 1-microglobulin. The detection limit of our method was 0.8 mg/l, enabling the application of the method for epidemiological investigations.

The importance of the intraindividual variability of renal function parameters used in occupational health

Various factors may influence the excretion of proteins and enzymes in urine. The intra‐individual variability of some urinary renal function parameters was determined in volunteers. The variability of albumin and total protein in urine was large. Men and women showed a different excretion of alanine aminopeptidase. For the estimation of individual risks on renal function disturbances, it is important to have more insight in the variability of renal function parameters and in the factors influencing these parameters.